The present invention is directed to an apparatus and method for delivering selected therapeutic and/or diagnostic agents to target sites in selected body tissues. More particularly, the invention provides for the needleless delivery of such agents by providing each agent in one or more high-energy jets or streams directed against selected wall or surface regions of selected tissues.
Needles have long been popular for delivering therapeutic and diagnostic agents into selected tissues. In a typical use, a needle, having an axial lumen extending therethrough, is passed through the wall of a selected tissue to a desired depth, and an agent is then passed from a holding region (e.g., in a bag, or syringe barrel), disposed in fluid communication with a proximal end of the needle, through the axial lumen and out of the distal end, into the tissue. Perhaps best known for their use in the delivery of agents through the skin, needles have also been widely employed in connection with catheters and endoscope-type devices for delivering agents to various organs and tissues within the body. For example, in a typical catheter-type device, an outer jacket is configured for navigation through a patient""s vasculature, e.g., using a pull-wire mechanism operable to deflect the distal-end region of the catheter, as desired. A reciprocally movable shaft, disposed within the jacket, defines an agent-delivery passage connected at its distal end to the proximal end of an agent-delivery needle. By advancing the internal shaft, an operator can cause the distal, pointed end of the needle to pierce a selected region of tissue. An agent can then be passed through the shaft""s lumen, e.g., under pressure, to flow out of the needle""s distal end and into the tissue.
While convenient and effective for certain purposes, the use of needles as injection devices is not without its disadvantages. For example, tissue damage can occur in the region of needle penetration. Also, as most needle-injection devices use only a single needle, the delivery of an agent thereby is often highly localized to one, relatively small region in the tissue (i.e., the site occupied by the needle""s distal end), thus limiting the area/volume of tissue that can be treated with each delivery operation. With particular regard to catheter-type needle-injection devices, such as described above, axial reciprocation of the needle-bearing shaft within the steerable jacket can be hampered, if not entirely prohibited, in situations where the distal-end region of the catheter must be deflected to a great degree, e.g., in efforts to reach remote regions via tortuous pathways of a patient""s vasculature, rendering such devices unsuitable for certain applications.
One aspect of the present invention provides an apparatus for delivering a selected diagnostic or therapeutic agent to a target site within a selected body tissue, such as myocardial tissue of the heart.
In one general embodiment, the apparatus includes an elongate jacket having (a) proximal and distal ends, (b) one or more lumens extending between such ends, and (c) a substantially blunt, distal-end face defining one or more outlet ports communicating with one or more of the lumens. Preferably, each outlet port has a diameter of about 0.025xe2x80x3, or less (e.g., from about 0.00025xe2x80x3 to about 0.020xe2x80x3). The apparatus further includes a pressure-control source (e.g., a pump) adapted for fluid communication with one or more of the lumens. The pressure-control source is operable to establish an elevated pressure (e.g., up to about 300 psi) within such lumen(s) such that an agent placed therein will be propelled toward, and out of, one or more of the outlet port(s), thereby forming one or more respective fluid jets or streams capable of penetrating a selected tissue disposed adjacent thereto.
The apparatus can further include one or more valves, such as spring-loaded needle-type plungers or the like, each being disposed at location along a distal region of a respective one of the lumens for regulating fluid flow therethrough. The valves can be manually operable, or they can respond automatically to one or more selected events (e.g., reaching a threshold pressure at or near a respective outlet port).
In one embodiment, at least one of the outlet ports has a central, longitudinal axis angled no greater than about 35xc2x0 in respect to a central, longitudinal axis of the jacket at its distal end. In another embodiment, the central, longitudinal axis of at least one of the outlet ports is oriented substantially parallel to the central, longitudinal axis of the jacket at its distal end. In a further embodiment, one or more outlet ports are configured to provide xe2x80x9cside firingxe2x80x9d fluid jets or streams.
The structure defining each lumen is configured to withstand an elevated pressure generated in the lumen. For example, in one embodiment, where the jacket defines a lumen, the jacket is adapted to withstand an internal pressure of at least about 300 psi along its proximal end, and at least about 100 psi along its distal end.
The pressure-control source can be a pump, such as a power injector or a hand-operable inflation device. Preferably, the pressure-control source is adapted to generate an internal pressure at a distal end of said jacket, proximate said outlet ports, of at least about 20 psi.
One embodiment of the apparatus incorporates the invention in a catheter-type device. For example, the jacket can be a flexible catheter jacket, including a steerable distal-end region that can be deflected in a manner permitting navigation through the vasculature of a subject body so that the outlet port(s) can be positioned adjacent a wall or surface region of a selected tissue or organ. Or, the catheter-type device can include a fixed shape (bend) at along its distal end to facilitate navigation. In yet another embodiment, a first steerable catheter is slidably maintained within an axial lumen of a second steerable catheter. Another embodiment of the apparatus incorporates the invention in an endoscope-type device. Another embodiment of the apparatus incorporates the invention in an open surgical tool having a bent head to access occluded regions of the tissue to be treated.
Any reasonable number of lumens can extend through the jacket of the apparatus. In one exemplary construction, at least two separate lumens extend through the jacket, each distally terminating at a fluid connection with at least one outlet port. For example, two or more separate lumens can be defined by respective elongate tubes extending through the jacket, with each tube having an internal passage with a diameter of from about 0.010xe2x80x3 to about 0.020xe2x80x3. Advantageously, this configuration reduces the dead volume in the system. Also, the xe2x80x9con/offxe2x80x9d response is optimized, and the pressure limit requirement for the conduit can be readily met.
The distal-end face of the jacket is defined, in one embodiment, by a plate-like member mounted substantially transverse to a longitudinal axis of the jacket at its distal-end region. Further in this embodiment, one or more bores extend through the plate-like memberxe2x80x94each defining an outlet port. In an exemplary construction, the plate-like member is formed of a suitable, non-reactive metal; and the bores are formed by laser drilling, and/or photo-chemical machining.
In one embodiment of the invention, the apparatus is embodied in a catheter-type assembly. An elongate catheter sleeve is provided, with the catheter sleeve having (i) proximal and distal ends, and (ii) one or more lumens between such ends. For navigation, the catheter sleeve can incorporate a fixed shape at its distal region, and/or it can incorporate a pull-wire steering mechanism. One of the lumens, in this embodiment, is adapted to removably receive the jacket.
According to one embodiment, the jacket-receiving lumen is further adapted to serve as a guidewire channel, when the jacket is removed therefrom.
In another embodiment, one of the lumens, other than the jacket-receiving lumen, defines a guidewire channel. In one exemplary arrangement, the jacket-receiving lumen and the guidewire channel extend side-by-side from the proximal end to the distal end of the catheter sleeve. In another exemplary arrangement, (i) the jacket-receiving lumen extends from the proximal end to the distal end of said sleeve, and (ii) the guidewire channel is provided near a distal end of the catheter sleeve to enable use of the apparatus as a rapid exchange type catheter.
One embodiment of the catheter-type apparatus further includes means for maintaining the distal end of the jacket at the selected target site within a patient""s body while one or more high-energy fluid jets or streams are being directed thereagainst.
A further aspect of the present invention provides an apparatus for delivering one or more selected diagnostic or therapeutic agents to a target site within a selected body tissue, including (i) an elongate jacket having (a) proximal and distal ends, (b) a lumen at least along the distal end of said jacket, and (c) a distal-end face defining one or more outlet ports communicating with said lumen; (ii) an agent-holding region (e.g., a chamber) adapted for fluid communication with said lumen; and (iii) means for moving such agent(s) from said holding region and through said outlet port(s) in a fashion effective to cause the agent(s) to penetrate a selected tissue disposed adjacent thereto.
In one embodiment, for use with one or more selected agents (e.g., DNA) coated on a plurality of carrier particles (e.g., gold particles), the moving means includes a biolistic particle-delivery or bombardment assembly disposed within a distal-end region of said jacket.
In another embodiment, the propelling means includes an ultrasonic transducer disposed across the lumen along a distal-end region of the jacket.
In yet another of its aspects, the present invention provides a method for delivering one or more selected diagnostic or therapeutic agents to a target site within a selected body organ or tissue. One general embodiment of the method includes the step of directing one or more fluid jets or streams against a wall or surface of a selected, internal body organ or tissue, with each jet or stream (i) carrying such agent(s), (ii) having a maximum diameter of about 0.025xe2x80x3, or less, as it contacts the wall or surface, and (iii) having an energy sufficient to permit the agent(s) to penetrate the organ or tissue to a depth of at least about 2 mm (preferably about 3-10 mm).
According to one embodiment, a gas is utilized as a partial injectate. For example, a gas can be included with one or more of the fluid jets or streams carrying one or more selected agents, or it can be directed therein from a secondary port. In one preferred embodiment, the gas is absorbable by the selected body organ or tissue. The gas, which can include, for example, CO2, can act as a good accelerator.
The method, as just set forth, can be effected using an agent-delivery apparatus comprised of an elongate jacket having (a) proximal and distal ends, (b) one or more lumens extending between such ends, and (c) a substantially blunt, distal-end face defining one or more outlet ports communicating with one or more of the lumens. The agent or agents are directed from the outlet port(s) against such wall or surface. In one embodiment, each jet or stream is formed by propelling the agent(s) through at least a portion of the lumen and out of one of the outlet ports under condition of an increased pressure at the port (e.g., up to about 100 psi; and preferably between about 20-30 psi).
One or more of the jets or streams can be directed substantially perpendicular to a wall or surface of the selected tissue, and/or they can be directed at an angle (e.g., no greater than about 35xc2x0 in respect to a line normal to a wall or surface of the tissue).
In one embodiment, the selected tissue is myocardial tissue, and the selected agent is directed against an endocardial wall, a septal wall, or an epicardial wall from a distance no greater than about 5 mm from such wall. Any desired agents can be employed (e.g., nucleic acids, proteins, etc.). For example, one or more agents can selected for desirable angiogenic properties. In one particular embodiment, the selected agent includes naked DNA.
These and other features and advantages of the present invention will become clear from the following description.